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Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut microbiota (GM) influences addictive behaviors, but the pattern of GM changes during addiction in animals of different species remains unclear. The aim of this study was to explore the association between dynamic changes in GM and MA self-administration acquisition among two classical mammals, rhesus monkeys (Macaca mulatta) and rats, MA self-administration models. Male Sprague-Dawley rats and male rhesus monkeys were subjected to classical MA self-administration training, and fecal samples were collected before and after MA self-administration training, respectively. 16S rRNA sequencing was used for GM analyses. We found that GM changes were more pronounced in rats than in rhesus monkeys, as evidenced by more GM taxa producing significant differences before and after MA self-administration training in rats than in monkeys. We also found that the expression of the genus Clostridia_vadinBB60_group significantly decreased after MA self-administration training in both rats and rhesus monkeys. Lactobacillus changes were significantly negatively correlated with total MA uptake in rats (Pearson R = - 0.666, p = 0.035; Spearman R = - 0.721, p = 0.023), whereas its change was also highly negatively correlated with total MA uptake in rhesus monkeys (Pearson R = - 0.882, p = 0.118; Spearman R = - 1.000, p = 0.083), although this was not significant. These findings suggest that MA causes significant alterations in GM in both rhesus monkeys and rats and that the genus Lactobacillus might be a common therapeutic target for MA uptake prevention across the species.
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Non-line-of-sight (NLOS) imaging has the ability to reconstruct hidden objects, allowing a wide range of applications. Existing NLOS systems rely on pulsed lasers and time-resolved single-photon detectors to capture the information encoded in the time of flight of scattered photons. Despite remarkable advances, the pulsed time-of-flight LIDAR approach has limited temporal resolution and struggles to detect the frequency-associated information directly. Here, we propose and demonstrate the coherent scheme-frequency-modulated continuous wave calibrated by optical frequency comb-for high-resolution NLOS imaging, velocimetry, and vibrometry. Our comb-calibrated coherent sensor presents a system temporal resolution at subpicosecond and its superior signal-to-noise ratio permits NLOS imaging of complex scenes under strong ambient light. We show the capability of NLOS localization and 3D imaging at submillimeter scale and demonstrate NLOS vibrometry sensing at an accuracy of dozen Hertz. Our approach unlocks the coherent LIDAR techniques for widespread use in imaging science and optical sensing.
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Objective: Pneumonia is a common and serious infectious disease that affects the older adult population. Severe pneumonia can lead to high mortality and morbidity in this group. Therefore, it is important to identify the risk factors and develop a prediction model for severe pneumonia in older adult patients. Method: In this study, we collected data from 1,000 older adult patients who were diagnosed with pneumonia and admitted to the intensive care unit (ICU) in a tertiary hospital. We used logistic regression and machine learning methods to analyze the risk factors and construct a prediction model for severe pneumonia in older adult patients. We evaluated the performance of the model using accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and calibration plot. Result: We found that age, comorbidities, vital signs, laboratory tests, and radiological findings were associated with severe pneumonia in older adult patients. The prediction model had an accuracy of 0.85, a sensitivity of 0.80, a specificity of 0.88, and an AUC of 0.90. The calibration plot showed good agreement between the predicted and observed probabilities of severe pneumonia. Conclusion: The prediction model can help clinicians to stratify the risk of severe pneumonia in older adult patients and provide timely and appropriate interventions.
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Unidades de Terapia Intensiva , Pneumonia , Humanos , Idoso , Feminino , Fatores de Risco , Masculino , Idoso de 80 Anos ou mais , Modelos Logísticos , Curva ROC , Índice de Gravidade de Doença , Aprendizado de Máquina , Medição de Risco/métodos , Comorbidade , Fatores Etários , Centros de Atenção TerciáriaRESUMO
Dormancy represents a fascinating adaptive strategy for organisms to survive in unforgiving environments. After a period of dormancy, organisms often exhibit exceptional resilience. This period is typically divided into hibernation and aestivation based on seasonal patterns. However, the mechanisms by which organisms adapt to their environments during dormancy, as well as the potential relationships between different states of dormancy, deserve further exploration. Here, we selected Perccottus glenii and Protopterus annectens as the primary subjects to study hibernation and aestivation, respectively. Based on histological and transcriptomic analysis of multiple organs, we discovered that dormancy involved a coordinated functional response across organs. Enrichment analyses revealed noteworthy disparities between the two dormant species in their responses to extreme temperatures. Notably, similarities in gene expression patterns pertaining to energy metabolism, neural activity, and biosynthesis were noted during hibernation, suggesting a potential correlation between hibernation and aestivation. To further explore the relationship between these two phenomena, we analyzed other dormancy-capable species using data from publicly available databases. This comparative analysis revealed that most orthologous genes involved in metabolism, cell proliferation, and neural function exhibited consistent expression patterns during dormancy, indicating that the observed similarity between hibernation and aestivation may be attributable to convergent evolution. In conclusion, this study enhances our comprehension of the dormancy phenomenon and offers new insights into the molecular mechanisms underpinning vertebrate dormancy.
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Estivação , Hibernação , Humanos , Animais , Estivação/genética , Peixes/genética , Perfilação da Expressão Gênica/veterinária , Transcriptoma , Hibernação/genéticaRESUMO
G protein-coupled receptor 39 (GPR39) senses the change of extracellular divalent zinc ion and signals through multiple G proteins to a broad spectrum of downstream effectors. Here, we found that GPR39 was prevalent at inhibitory synapses of spinal cord somatostatin-positive (SOM+) interneurons, a mechanosensitive subpopulation that is critical for the conveyance of mechanical pain. GPR39 complexed specifically with inhibitory glycine receptors (GlyRs) and helped maintain glycinergic transmission in a manner independent of G protein signalings. Targeted knockdown of GPR39 in SOM+ interneurons reduced the glycinergic inhibition and facilitated the excitatory output from SOM+ interneurons to spinoparabrachial neurons that engaged superspinal neural circuits encoding both the sensory discriminative and affective motivational domains of pain experience. Our data showed that pharmacological activation of GPR39 or augmenting GPR39 interaction with GlyRs at the spinal level effectively alleviated the sensory and affective pain induced by complete Freund's adjuvant and implicated GPR39 as a promising therapeutic target for the treatment of inflammatory mechanical pain.
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Dor , Receptores Acoplados a Proteínas G , Humanos , Neurônios/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Glicina/metabolismo , Transdução de Sinais , Medula Espinal/metabolismoRESUMO
DPY30 belongs to the core subunit of components of the histone lysine methyltransferase complex, which is implicated in tumorigenesis, cell senescence, and other biological events. However, its contribution to colorectal carcinoma (CRC) progression and metastasis has yet to be elucidated. Therefore, this study aimed to investigate the biological function of DPY30 in CRC metastasis both in vitro and in vivo. Herein, our results revealed that DPY30 overexpression is significantly positively correlated with positive lymph nodes, epithelial-mesenchymal transition (EMT), and CRC metastasis. Moreover, DPY30 knockdown in HT29 and SW480 cells markedly decreased EMT progression, as well as the migratory and invasive abilities of CRC cells in vitro and lung tumor metastasis in vivo. Mechanistically, DPY30 increased histone H3K4me3 level and promoted EMT and CRC metastasis by upregulating the transcriptional expression of ZEB1. Taken together, our findings indicate that DPY30 may serve as a therapeutic target and prognostic marker for CRC.
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IMPORTANCE: Aquaculture is essential for ensuring global food security by providing a significant source of animal protein. However, the spread of the white spot syndrome virus (WSSV) has resulted in considerable economic losses in crustacean industries. In this study, we evaluated the antiviral activity of rhein, the primary bioactive component of Rheum palmatum L., against WSSV infection, and many pathological aspects of WSSV were also described for the first time. Our mechanistic studies indicated that rhein effectively arrested the replication of WSSV in crayfish by modulating innate immunity to inhibit viral gene transcription. Furthermore, we observed that rhein attenuated WSSV-induced oxidative and inflammatory stresses by regulating the expression of antioxidant and anti-inflammatory-related genes while enhancing innate immunity by reducing total protein levels and increasing phosphatase activity. Our findings suggest that rhein holds great promise as a potent antiviral agent for the prevention and treatment of WSSV in aquaculture.
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Astacoidea , Vírus da Síndrome da Mancha Branca 1 , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Vírus da Síndrome da Mancha Branca 1/genética , Imunidade Inata , Antivirais/farmacologiaRESUMO
DPY30, a core subunit of the SET1/MLL histone H3K4 methyltransferase complexes, plays an important role in diverse biological functions through the epigenetic regulation of gene transcription, especially in cancer development. However, its involvement in human colorectal carcinoma (CRC) has not been elucidated yet. Here we demonstrated that DPY30 was overexpressed in CRC tissues, and significantly associated with pathological grading, tumor size, TNM stage, and tumor location. Furthermore, DPY30 knockdown remarkably suppressed the CRC cell proliferation through downregulation of PCNA and Ki67 in vitro and in vivo, simultaneously induced cell cycle arrest at S phase by downregulating Cyclin A2. In the mechanistic study, RNA-Seq analysis revealed that enriched gene ontology of cell proliferation and cell growth was significantly affected. And ChIP result indicated that DPY30 knockdown inhibited H3 lysine 4 trimethylation (H3K4me3) and attenuated interactions between H3K4me3 with PCNA, Ki67 and cyclin A2 respectively, which led to the decrease of H3K4me3 establishment on their promoter regions. Taken together, our results demonstrate overexpression of DPY30 promotes CRC cell proliferation and cell cycle progression by facilitating the transcription of PCNA, Ki67 and cyclin A2 via mediating H3K4me3. It suggests that DPY30 may serve as a potential therapeutic molecular target for CRC.
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Neoplasias Colorretais , Ciclina A2 , Humanos , Ciclina A2/genética , Fatores de Transcrição , Epigênese Genética , Antígeno Ki-67 , Antígeno Nuclear de Célula em Proliferação , Proliferação de Células/genética , Ciclo Celular/genética , Neoplasias Colorretais/genéticaRESUMO
BACKGROUND: The failure of novel therapies effective in preclinical animal models largely reflects the fact that current models do not really mimic the pathological/therapeutic features of glioblastoma (GBM), in which the most effective temozolomide chemoradiotherapy (RT/TMZ) regimen can only slightly extend survival. How to improve RT/TMZ efficacy remains a major challenge in clinic. METHODS: Syngeneic G422TN-GBM model mice were subject to RT/TMZ, surgery, piperlongumine (PL), αPD1, glutathione. Metabolomics or transcriptomics data from G422TN-GBM and human GBM were used for gene enrichment analysis and estimation of ROS generation/scavenging balance, oxidative stress damage, inflammation and immune cell infiltration. Overall survival, bioluminescent imaging, immunohistochemistry, and immunofluorescence staining were used to examine therapeutic efficacy and mechanisms of action. RESULTS: Here we identified that glutathione metabolism was most significantly altered in metabolomics analysis upon RT/TMZ therapies in a truly refractory and reliable mouse triple-negative GBM (G422TN) preclinical model. Consistently, ROS generators/scavengers were highly dysregulated in both G422TN-tumor and human GBM. The ROS-inducer PL synergized surgery/TMZ, surgery/RT/TMZ or RT/TMZ to achieve long-term survival (LTS) in G422TN-mice, but only one LTS-mouse from RT/TMZ/PL therapy passed the rechallenging phase (immune cure). Furthermore, the immunotherapy of RT/TMZ/PL plus anti-PD-1 antibody (αPD1) doubled LTS (50%) and immune-cured (25%) mice. Glutathione completely abolished PL-synergistic effects. Mechanistically, ROS reduction was associated with RT/TMZ-resistance. PL restored ROS level (mainly via reversing Duox2/Gpx2), activated oxidative stress/inflammation/immune responses signature genes, reduced cancer cell proliferation/invasion, increased apoptosis and CD3+/CD4+/CD8+ T-lymphocytes in G422TN-tumor on the basis of RT/TMZ regimen. CONCLUSION: Our findings demonstrate that PL reverses RT/TMZ-reduced ROS and synergistically resets tumor microenvironment to cure GBM. RT/TMZ/PL or RT/TMZ/PL/αPD1 exacts effective immune cure in refractory GBM, deserving a priority for clinical trials.
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Glioblastoma , Glioma , Humanos , Animais , Camundongos , Glioblastoma/tratamento farmacológico , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Espécies Reativas de Oxigênio , Linfócitos T CD8-Positivos , Estresse Oxidativo , Quimiorradioterapia , Microambiente TumoralRESUMO
The discovery of neuroglobin (Ngb), a brain- or neuron-specific member of the hemoglobin family, has revolutionized our understanding of brain oxygen metabolism. Currently, how Ngb plays such a role remains far from clear. Here, we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia. We found that Ngb was present in, co-localized to, and co-migrated with mitochondria in the cell body and neurites of neurons. Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane (CM) or cell surface in living neurons, and this was accompanied by the mitochondria. In vivo, hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasm/mitochondria ratio. Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase (SDH) and ATPase activity in neuronal N2a cells. Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia. Mutation of Ngb at its oxygen-binding site (His64) significantly increased SDH activity and reduced ATPase activity in N2a cells. Taken together, Ngb was physically and functionally linked to mitochondria. In response to an insufficient oxygen supply, Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation. This novel mechanism of neuronal respiration provides new insights into the understanding and treatment of neurological diseases such as stroke and Alzheimer's disease and diseases that cause hypoxia in the brain such as anemia.
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Anemia , Globinas , Ratos , Animais , Neuroglobina/metabolismo , Globinas/genética , Globinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Hipóxia/metabolismo , Encéfalo/metabolismo , Oxigênio , Anemia/metabolismo , Adenosina Trifosfatases/metabolismoRESUMO
Networks of optical clocks find applications in precise navigation1,2, in efforts to redefine the fundamental unit of the 'second'3-6 and in gravitational tests7. As the frequency instability for state-of-the-art optical clocks has reached the 10-19 level8,9, the vision of a global-scale optical network that achieves comparable performances requires the dissemination of time and frequency over a long-distance free-space link with a similar instability of 10-19. However, previous attempts at free-space dissemination of time and frequency at high precision did not extend beyond dozens of kilometres10,11. Here we report time-frequency dissemination with an offset of 6.3 × 10-20 ± 3.4 × 10-19 and an instability of less than 4 × 10-19 at 10,000 s through a free-space link of 113 km. Key technologies essential to this achievement include the deployment of high-power frequency combs, high-stability and high-efficiency optical transceiver systems and efficient linear optical sampling. We observe that the stability we have reached is retained for channel losses up to 89 dB. The technique we report can not only be directly used in ground-based applications, but could also lay the groundwork for future satellite time-frequency dissemination.
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The outbreak of white spot syndrome (WSS) is a looming challenge, due to dramatic losses to the crustacean aquaculture industry. However, at present, there are no prophylactic or therapeutic means to control this infectious viral disease. Here, we screened fifteen medicinal plants for their inhibitory activity on the white spot syndrome virus (WSSV), using red swamp crayfish (Procambarus clarkii) as a model species. The results showed that the crude extracts of Pinellia ternata (Thunb.) Breit. had the highest inhibitory effect (91.59%, 100 mg/kg) on WSSV proliferation, and its main component, beta-sitosterol, showed a much higher activity (95.79%, 50 mg/kg). Further, beta-sitosterol potently reduced (p < 0.01) viral loads and viral gene transcription levels in a concentration-dependent fashion, and significantly promoted the survival rate of WSSV-challenged crayfish (57.14%, 50 mg/kg). The co-incubation assay indicated that beta-sitosterol did not influence the infectivity of WSSV particles. Both pre- and post-treatment of beta-sitosterol exerted a significant inhibitory effect (p < 0.01) on the viral load in vivo. Mechanistically, beta-sitosterol not only interfered with the expression of viral genes (immediate early gene 1, ie1; DNA polymerase, DNApol) that are important in initiating WSSV transcription, but it also attenuated the hijacking of innate immune signaling pathways (Toll, IMD, and JAK/STAT pathways) by viral genes to block WSSV replication. Moreover, the expression of several antiviral immune, antioxidant, pro-inflammatory, and apoptosis-related genes changed significantly in beta-sitosterol-treated crayfish. Beta-sitosterol is a potent WSSV inhibitor and has the potential to be developed as an effective anti-WSSV agent against a WSS outbreak in crustacean aquaculture.
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Vírus da Síndrome da Mancha Branca 1 , Animais , Antioxidantes/farmacologia , Antivirais/farmacologia , Astacoidea/genética , Misturas Complexas/farmacologia , SitosteroidesRESUMO
Nocardiosis caused by Nocardia seriolae is a major threat to the aquaculture industry. Given that prolonged therapy administration can lead to a growth of antibiotic resistant strains, new antibacterial agents and alternative strategies are urgently needed. In this study, 80 medicinal plants were selected for antibacterial screening to obtain potent bioactive compounds against N. seriolae infection. The methanolic extracts of Magnolia officinalis exhibited the strongest antibacterial activity against N. seriolae with the minimal inhibitory concentration (MIC) of 12.5 µg/ml. Honokiol and magnolol as the main bioactive components of M. officinalis showed higher activity with the MIC value of 3.12 and 6.25 µg/ml, respectively. Sequentially, the evaluation of antibacterial activity of honokiol in vivo showed that honokiol had good biosafety, and could significantly reduce the bacterial load of nocardia-infected largemouth bass (p < .001). Furthermore, the survival rate of nocardia-infected fish fed with 100 mg/kg honokiol was obviously improved (p < .05). Collectively, these results suggest that medicinal plants represent a promising reservoir for discovering active components against Nocardia, and honokiol has great potential to be developed as therapeutic agents to control nocardiosis in aquaculture.
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Bass , Doenças dos Peixes , Magnolia , Nocardiose , Nocardia , Plantas Medicinais , Compostos Alílicos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Compostos de Bifenilo , Doenças dos Peixes/tratamento farmacológico , Nocardiose/tratamento farmacológico , Nocardiose/veterinária , Fenóis , Extratos Vegetais/farmacologiaRESUMO
White spot syndrome virus (WSSV) is a fatal pathogen threatening global crustacean industry with no commercially available drugs to control. Herbal medicines have been widely used to treat a number of viral infections, which could offer a rich reserve for antiviral drug discovery. Here, we evaluated the inhibition activities of 30 herbal medicines against WSSV in Chinese mitten crab Eriocheir sinensis. A WSSV infection model in E. sinensis was firstly established in order to determine the antiviral effects of the plant extracts and to explore the potential action mechanisms. Results showed that the highest anti-WSSV activity was obtained by the treatment of Ophiopogon japonicus extract (93.03%, 100 mg/kg). O. japonicus treatment decreased viral loads in a dose-dependent manner and significantly improved the survival of WSSV-challenged crabs. O. japonicus reduced the expression of vital genes in viral life cycle in vivo, particularly for the immediate-early stage gene ie1. Further results indicated that O. japonicus could repress the JAK-STAT signaling pathway to block ie1 transcription. Moreover, O. japonicus could modulate certain immune genes such as the myosin, toll-like receptor, crustin, and prophenoloxidase in the interactions between WSSV and crabs. The up-regulated expression of pro-autophagic factors (Gabarap and Atg7) and elevated levels of antioxidant enzymes (SOD, CAT and GSH) suggested that O. japonicus may induce autophagy and attenuate WSSV-induced oxidative stress. Taken together, O. japonicus could inhibit WSSV proliferation and improve the survival of WSSV-challenged crabs. Thus, O. japonicus may have the potential to be developed as a preventive or therapeutic agent against WSSV, and its effective compounds merit further isolation and identification.
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Ophiopogon , Vírus da Síndrome da Mancha Branca 1 , Animais , Antivirais , Proteínas de Artrópodes/genética , Proliferação de Células , China , Imunidade InataRESUMO
White spot syndrome virus (WSSV) is a fatal pathogen threatening global crustacean industry with no commercially available drugs to control WSSV. To address the urgent need for finding effective antiviral agents against WSSV, we examined the anti-WSSV activities of 11 common antiviral agents in crayfish Procambarus clarkia. The results showed that acyclovir displayed the highest inhibition on WSSV replication in vivo (92.59%, 50 mg/kg). Acyclovir repressed WSSV proliferation followed a dose-dependent fashion and pre- or post-treatment of acyclovir exerted strong inhibition on the viral loads. Further, we observed a markedly reduced expression levels of WSSV genes (immediate-early IE gene ie1, DNA polymerase gene DNApol and envelope protein gene Vp28) that are crucial in viral life cycle with the acyclovir treatment during the early infection. Meantime, we also found a significantly increased expressions of anti-oxidative as well as apoptosis related genes, suggesting that acyclovir could effectively suppress WSSV replication in vivo. Finally, acyclovir treatment could significantly improve the survival rate of WSSV-challenged crayfish by 56%. Taken together, acyclovir has the potential to be developed as a promising preventive or therapeutic agent against WSSV infection, and this finding may provide a reference for rapid discovery anti-WSSV agent in crustacean aquaculture.
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Vírus da Síndrome da Mancha Branca 1 , Aciclovir/farmacologia , Animais , Antivirais/farmacologia , Astacoidea , Genes Precoces , Replicação Viral , Vírus da Síndrome da Mancha Branca 1/genéticaRESUMO
White spot syndrome virus (WSSV) is a serious pathogen threatening global crustacean aquaculture with no commercially available drugs. Herbal medicines widely used in antiviral research offer a rich reserve for drug discovery. Here, we investigated the inhibitory activity of 13 herbal medicines against WSSV in crayfish Procambarus clarkii and discovered that naringenin (NAR) has potent anti-WSSV activity. In the preliminary screening, the extracts of Typha angustifolia displayed the highest inhibitory activity on WSSV replication (84.62%, 100 mg/kg). Further, NAR, the main active compound of T. angustifolia, showed a much higher inhibition rate (92.85%, 50 mg/kg). NAR repressed WSSV proliferation followed a dose-dependent manner and significantly improved the survival of WSSV-challenged crayfish. Moreover, pre- or post-treatment of NAR displayed a comparable inhibition on the viral loads. NAR decreased the transcriptional levels of vital genes in viral life cycle, particularly for the immediately early-stage gene ie1. Further results showed that NAR could decrease the STAT gene expression to block ie1 transcription. Besides, NAR modulated immune-related gene Hsp70, antioxidant (cMnSOD, mMnSOD, CAT, GST), anti-inflammatory (COX-1, COX-2) and pro-apoptosis-related factors (Bax and BI-1) to inhibit WSSV replication. Overall, these results suggest that NAR may have the potential to be developed as preventive or therapeutic agent against WSSV.
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Antivirais/farmacologia , Astacoidea/virologia , Flavanonas/farmacologia , Typhaceae/química , Vírus da Síndrome da Mancha Branca 1/efeitos dos fármacos , Animais , Antivirais/química , Flavanonas/química , Replicação Viral/efeitos dos fármacos , Vírus da Síndrome da Mancha Branca 1/fisiologiaRESUMO
Overexpression of extracellular signal-regulated kinase ½ (ERK ½) signaling pathway leads to overproduction of reactive oxygen species (ROS) which induces oxidative stress. Coenzyme Q10 (CoQ10) scavenges ROS and protects cells against oxidative stress. The present study was designed to examine whether the protection of Coenzyme Q10 against oxidative damage in astrocytes is through regulating ERK 1/2 pathway. Ultraviolet B (UVB) irradiation was chosen as a tool to induce oxidative stress. Murine astrocytes were treated with 10 µg/ml and 25 µg/ml of CoQ10 for 24 h prior to UVB and maintained during UVB and 24 h post-UVB. Cell viability was evaluated by counting viable cells and MTT conversion assay. ROS production was measured using fluorescent probes. Levels of p-ERK 1/2, ERK 1/2, p-PKA, PKA were detected using immunocytochemistry and/or Western blotting. The results showed that UVB irradiation decreased the number of viable cells. This damaging effect was associated with accumulation of ROS and elevations of p-ERK 1/2 and p-PKA. Treatment with CoQ10 at 25 µg/ml significantly increased the number of viable cells and prevented the UVB-induced increases of ROS, p-ERK 1/2, and p-PKA. It is concluded that suppression of the PKA-ERK 1/2 signaling pathway may be one of the important mechanisms by which CoQ10 protects astrocytes from UVB-induced oxidative damage.
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Astrócitos/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Estresse Oxidativo/efeitos da radiação , Protetores contra Radiação/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ubiquinona/análogos & derivados , Animais , Astrócitos/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Camundongos , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Succinato Desidrogenase/metabolismo , Ubiquinona/farmacologia , Raios UltravioletaRESUMO
Chirality represents a kind of symmetry breaking characterized by the noncoincidence of an object with its mirror image and has been attracting intense attention in a broad range of scientific areas. The recent realization of spin-orbit coupling in ultracold atomic gases provides a new perspective to study quantum states with chirality. In this Letter, we demonstrate that the combined effects of spin-orbit coupling and interatomic soft-core long-range interaction can induce an exotic supersolid phase in which the chiral symmetry is broken with spontaneous emergence of circulating particle current. This implies that a finite angular momentum can be generated with neither rotation nor effective magnetic field. The direction of the angular momentum can be altered by adjusting the strength of spin-orbit coupling or interatomic interaction. The predicted chiral supersolid phase can be experimentally observed in Rydberg-dressed Bose-Einstein condensates with spin-orbit coupling.
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The abuse of amphetamine-type stimulants (ATS) has become a global public health issue in recent years, these new-type drugs can cause addiction and serious cognitive impairment. However, there are no effective methods for the prevention and treatment of ATS addiction at present. Repetitive transcranial magnetic stimulation (rTMS) is a painless and non-invasive new therapeutic approach that has been used for the treatment of depression and other neuropsychiatric disorders, but whether it can be used to treat drug addiction is unclear. In the present study, we investigated the possible effects of rTMS on methamphetamine(METH)-induced conditioned place preference (CPP). High-frequency (10â¯Hz) and low-frequency stimulation patterns (1â¯Hz) were applied to test the effect of rTMS on METH-induced CPP. The results showed that low-frequency but not high-frequency rTMS could block METH-CPP, accompanied with a downregulation of gamma-aminobutyric acid type B receptor subunit 1 (GABABR1) expression in rat dorsolateral striatum. These results suggested that low-frequency rTMS could effectively inhibit the development of METH addiction and shed light on the rTMS as a potential approach for the prevention of drug addiction.
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Transtornos Relacionados ao Uso de Anfetaminas/prevenção & controle , Estimulação Magnética Transcraniana , Transtornos Relacionados ao Uso de Anfetaminas/fisiopatologia , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Expressão Gênica/fisiologia , Masculino , Metanfetamina/farmacologia , Distribuição Aleatória , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismo , Comportamento Espacial/efeitos dos fármacos , Comportamento Espacial/fisiologia , Estimulação Magnética Transcraniana/métodosRESUMO
Although it has been reported that polysaccharides found in Lycium barbarum possess neuroprotective effects, little is known of their ability to ameliorate hyperglycemia-aggravated ischemia/reperfusion brain injury. In this study, normoglycemic (NG) and hyperglycemic (HG) rats were compared after 30 minutes of middle cerebral artery occlusion (MCAO), followed by 24 or 27 hours of reperfusion, with HG rats pretreated with lyceum barbarum polysaccharides (LBP) or insulin. In each group, the neurological deficit, infarct volume, pathohistology, and expression of proteins, Opa1 and Drp1, were assessed to determine the efficacy of LBP in alleviating hyperglycemia-aggravated ischemia/reperfusion brain injury. Our results show that, compared to the NG group, the HG group had increases in neurological deficits, infarct volume, and evidence of neuronal pyknosis at 24- and/or 72-h of reperfusion (P<0.05) and that pre-treatment with LBP decreased these effects (P<0.05). In addition, immunohistochemistry revealed an increase of Drp1 and a decrease of Opa1 positive neurons in the HG group after 24 and 72 hours of reperfusion when compared to the NG group. LBP treatment prevented the HG-induced alterations in Drp-1 and Opa1 expression. Western blots further confirmed these findings showing that HG caused an increase in phospho-Drp1 and a decrease in Opa1 which were subsequently reversed by LBP addition. These results suggest that hyperglycemia-aggravated ischemic brain damage is associated with an alteration of mitochondrial dynamics and that pre-treatment with LBP ameliorates the hyperglycemia-enhanced ischemic brain damage through maintaining mitochondrial dynamic balance.